Tregs and allergic disease
Douglas S. Robinson, Mark Larché, Stephen R. Durham
Douglas S. Robinson, Mark Larché, Stephen R. Durham
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Tregs and allergic disease

Abstract

Allergic diseases such as asthma, rhinitis, and eczema are increasing in prevalence and affect up to 15% of populations in Westernized countries. The description of Tregs as T cells that prevent development of autoimmune disease led to considerable interest in whether these Tregs were also normally involved in prevention of sensitization to allergens and whether it might be possible to manipulate Tregs for the therapy of allergic disease. Current data suggest that Th2 responses to allergens are normally suppressed by both CD4+CD25+ Tregs and IL-10 Tregs. Furthermore, suppression by these subsets is decreased in allergic individuals. In animal models, Tregs could be induced by high- or low-dose inhaled antigen, and prior induction of such Tregs prevented subsequent development of allergen sensitization and airway inflammation in inhaled challenge models. For many years, allergen-injection immunotherapy has been used for the therapy of allergic disease, and this treatment may induce IL-10 Tregs, leading to both suppression of Th2 responses and a switch from IgE to IgG4 antibody production. Improvements in allergen immunotherapy, such as peptide therapy, and greater understanding of the biology of Tregs hold great promise for the treatment and prevention of allergic disease.

Authors

Douglas S. Robinson, Mark Larché, Stephen R. Durham

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Figure 1

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Peripheral blood CD4+CD25+ T cells from atopic volunteers show reduced s...
Peripheral blood CD4+CD25+ T cells from atopic volunteers show reduced suppressive ability in allergen-stimulated T cell cultures. CD4+CD25– T cells were separated from peripheral blood by immunomagnetic separation, then cultured with allergen extracts either alone or mixed with CD4+CD25+ T cells. Proliferation was assessed by incorporation of tritiated thymidine (shown as cpm), and IL-5 was measured in supernatants at day 6 of cultures by Luminex bead array. Data shown are means and standard errors for cpm and IL-5 from 9 separate nonatopic donors, showing almost complete suppression of responses of CD4+CD25– T cells when CD4+CD25+ T cells were added. When these data were expressed as percentage suppression (reduction in counts in the mixed culture compared with those in CD4+CD25– T cells alone), suppression was significantly less when cells were obtained from atopic donors or volunteers with hay fever studied in or out of season (IS or OS). Suppression out of season was significantly more than that seen in season but still significantly less than in nonatopic controls. Figure adapted from Lancet (54), with permission from Elsevier.